The southern Big Bend of the San Andreas fault (SAF) accommodates transpression along numerous non‐vertical, non‐planar, and intersecting active surfaces. Using three‐dimensional boundary element method (BEM) models, we test the sensitivity of fault slip rates to a range of tectonic boundary conditions constrained by Global Positioning System (GPS) studies of the region (45–50 mm/yr and 320°–325°). Using this approach, our models provide a range of distributed fault slip rates associated with both spatial variations in geometry and present‐day uncertainties in plate motion. Model slip rates match most of the available geologic slip rates, and discrepancies may owe to inaccurate fault geometries. More northerly plate velocity (325°) produces greater transpression along the SAF system associated with greater uplift of the San Bernardino Mountains, greater reverse‐slip rates along range bounding reverse thrust faults, lower strike‐slip rates along the San Andreas and San Jacinto faults, and greater strike‐slip rates along the Eastern California Shear Zone (ECSZ) and Garlock fault. These results suggest that the degree of regional transpression controls the partitioning of deformation between uplift, and slip along both the SAF system and the ECSZ. The insensitivity of modeled slip rates to applied velocity along the southern San Andreas and San Jacinto faults suggests that fault geometry greatly influences slip rates within the San Bernardino Mountains region. A northerly shift in plate velocity orientation could account for the abandonment of the Mill Creek strand of the SAF>95 ka and development of the present‐day active geometry, which accommodates greater uplift.